Non‐invasive molecular detection of bladder cancer recurrence

Abstract

Transitional cell carcinoma (TCC) is the most common bladder tumor and Ϸ90% of bladder TCC are superficial at initial diagnosis. High recurrence rate and possible progression to muscle invasive disease that is eventually indicated for radical cystectomy are established features of these tumors. Therefore, reliable predictors of tumor recurrence are of critical importance for management of superficial bladder TCC. Successful molecular diagnosis of bladder cancer by detecting genetic lesions: loss of heterozygosity (LOH) or microsatellite instability (MSI) in cells exfoliated in urine has been reported by several groups including ours. The aim of our study was to evaluate the predictive potential of microsatellite analysis of cells exfoliated in urine in the detection of superficial bladder TCC recurrence. We studied 47 Caucasian patients with confirmed superficial bladder TCC (37 pTa, 10 pT1) at initial diagnosis. Blood samples were obtained once from every patient whereas urine samples were collected before each cystoscopy (initial and follow-up). Matched DNAs from blood and urine were subjected to microsatellite analysis in a blinded fashion. The follow-up period ranged 12-48 months after tumor resection. Microsatellite analysis correctly identified 94% (44/47) of primary tumors and 92% (12/13) of tumor recurrences. Interestingly enough, 75% (9/12) of tumor recurrences were molecularly detected 1-9 months before cystoscopic evidence of recurrent disease. This study demonstrated clearly that not only urine microsatellite analysis reliably detected superficial bladder tumors, but also was a reliable test for detecting and predicting tumor recurrence in Caucasian patients. These results warrant multicenter randomized trials.

Molecular Detection of Noninvasive and Invasive Bladder Tumor Tissues and Exfoliated Cells by Aberrant Promoter Methylation of Laminin-5 Encoding Genes

“…TCCs are subdivided into noninvasive papillary and nonpapillary invasive carcinoma types. Papillary TCCs correspond to 70% of all of the TCCs and usually are low grade, superficial, and noninvasive at the time of presentation (1)(2)(3). Papillary TCCs are characterized by high rates of recurrence, and ϳ10 -30% will progress eventually to invasive disease (3)(4)(5).…”

“…Bladder carcinoma is the most common urothelial malignancy and occupies the 5th and the 10th ranks of neoplasms in men and women, respectively, in more developed countries (1). Histologically, ϳ90% of bladder carcinomas are urothelial carcinomas, characterized by malignant proliferation of the transitional epithelium [transitional cell carcinomas (TCCs)].…”

Intestinal type villous adenoma of the renal pelvis

“…12 The molecular pathogenesis of these inherited tumours is related to defects in the genes encoding the DNA mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. 13 Sporadic and inherited defects in the mismatch repair genes are also implicated in about 15% of colorectal adenocarcinomas. 12 Given that this villous adenoma has the unusual combination of location in the upper urothelial tract and morphologic similarity to colorectal dysplasia and adenocarcinoma, we hypothesized that a defect in mismatch repair proteins may be present.…”

Patients’ perceived burden of cystoscopic and urinary surveillance of bladder cancer: a randomized comparison

“…A few empirical studies compared the efficiency of CUS and MA of voided urine samples to detect bladder cancer recurrences. Both Van Rhijn et al [10] and Amira et al [11] reported a lower sensitivity for MA than for CUS. In particular, MA missed a few low-grade, low-stage bladder tumours.…”